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Genetic Lipoprotein Disorders and Cardiovascular Disease

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Clinical Approach to Sudden Cardiac Death Syndromes

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Abstract

Plasma (or serum) levels of lipids and lipoprotein lipids have proven among the most potent and best substantiated risk factors for atherosclerosis in general and coronary heart disease (CHD) in particular. The present chapter deals with the fundamentals of lipid metabolism, the genetic lipoprotein disorders, and a practical approach to their diagnosis.

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Abbreviations

ABCA1:

ATP-binding cassette transporter A1

ABCG1:

ATP-binding cassette transporter G1

ACAT:

Acetyl-CoA acetyltransferase

Apo:

Apolipoprotein

ApoBec:

Apo B editing complex

C:

Cholesterol

CE:

Cholesteryl ester

CETP:

Cholesteryl ester transfer protein

CoA:

Coenzyme A

EL:

Endothelial lipase

FFA:

Free fatty acids

HDL:

High-density lipoprotein

HL:

Hepatic lipase

HMG CoA Red:

Hydroxymethylglutaryl coenzyme A reductase

HSL:

Hormone-sensitive lipase

IDL:

Intermediate-density lipoprotein

IDL:

Intermediate-density lipoprotein

LCAT:

Lecithin cholesterol acyltransferase

LDL:

Low-density lipoprotein

LDL-R:

Low-density lipoprotein receptor

Lp(a):

Lipoprotein (a)

LRP:

Low-density lipoprotein receptor- related peptide

NPC1L1:

Niemann-Pick disease type C protein (NPC) like 1

PLTP:

Phospholipid transfer protein

PLTP:

Phospholipid transfer protein

sER:

Smooth endoplasmic reticulum

SR- B1:

Scavenger receptor B1

TG:

Triglycerides

TIA:

Transient ischemic attack

TRL:

Triglyceride-rich lipoproteins

VLDL:

Very-low-density lipoprotein

VLDL-R:

Very-low-density lipoprotein receptor

References

  1. Ajees AA, Anantharamaiah GM, Mishra VK, Hussain MM, Murthy HM (2006) Crystal structure of human apolipoprotein A-I: insights into its protective effect against cardiovascular diseases. Proc Natl Acad Sci USA 103(7):2126-2131

    Article  CAS  PubMed  Google Scholar 

  2. Hiltunen TP, Luoma JS, Nikkari T, Yla-Herttuala S (1998) Expression of LDL receptor, VLDL receptor, LDL receptor-related protein, and scavenger receptor in rabbit atherosclerotic lesions: Marked induction of scavenger receptor and VLDL receptor expression during lesion development. Circulation 97:1079

    CAS  PubMed  Google Scholar 

  3. MacDougall ED, Kramer F, Polinsky P, Barnhart S, Askari B, Johansson F, Varon R, Rosenfeld ME, Oka K, Chan L, Schwartz SM, Bornfeldt KE (2006) Aggressive very low-density lipoprotein (VLDL) and LDL lowering by gene transfer of the VLDL receptor combined with a low-fat diet regimen induces regression and reduces macrophage content in advanced atherosclerotic lesions in LDL receptor-deficient mice. Am J Pathol 168(6):2064-2073

    Article  CAS  PubMed  Google Scholar 

  4. Mahley RW, Ji ZS (1999) Remnant lipoprotein metabolism: key pathways involving cell-surface heparan sulfate proteoglycans and apolipoprotein E. J Lipid Res 40:1

    CAS  PubMed  Google Scholar 

  5. Brown ML, Ramprasad MP, Umeda PK et al. (2000) A macrophage receptor for apolipoprotein B48: cloning, expression, and atherosclerosis. Proc Natl Acad Sci USA 97:7488

    Article  CAS  PubMed  Google Scholar 

  6. Spillmann D, Lookene A, Olivecrona G. Isolation and characterization of low sulfated heparan sulfate sequences with affinity for lipoprotein lipase. J Biol Chem. 2006 June 16; [Epub ahead of print]

    Google Scholar 

  7. Sawamura T, Kume N, Aoyama T et al. (1997) An endothelial receptor for oxidized low-density lipoprotein. Nature 386:73

    Article  CAS  PubMed  Google Scholar 

  8. Acton S, Rigotti A, Landschulz KT et al. (1996) Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science 271:518

    Article  CAS  PubMed  Google Scholar 

  9. Krimbou L, Hassan HH, Blain S et al. (2005) Biogenesis and speciation of nascent apo AI - containing particles in various cell lines. J Lipid Res 46:1668-1677

    Article  CAS  PubMed  Google Scholar 

  10. Altmann SW, Davis HR Jr, Zhu LJ et al. (2004) Niemann-Pick C1 like 1 protein is critical for intestinal cholesterol absorption. Science 303:1201

    Article  CAS  PubMed  Google Scholar 

  11. Abifadel M, Varret M, Rabes JP et al. (2003) Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 34:154

    Article  CAS  PubMed  Google Scholar 

  12. Willner EL, Tow B, Buhman KK et al. (2003) Deficiency of acyl CoA:cholesterol acyltransferase 2 prevents atherosclerosis in apolipoprotein E-deficient mice. Proc Natl Acad Sci USA 100:1262

    Article  CAS  PubMed  Google Scholar 

  13. Timmins JM, Lee JY, Boudyguina E et al. (2005) Targeted inactivation of hepatic Abca1 causes profound hypoalphalipoproteinemia and kidney hypercatabolism of apoA-I. J Clin Invest 115(5):1333-1342

    CAS  PubMed  Google Scholar 

  14. Brunham LR, Kruit JK, Iqbal J, Fievet C, Timmins JM, Pape TD, Coburn BA, Bissada N, Staels B, Groen AK, Hussain MM, Parks JS, Kuipers F, Hayden MR (2006) Intestinal ABCA1 directly contributes to HDL biogenesis in vivo. J Clin Invest 116(4):1052-1062

    Article  CAS  PubMed  Google Scholar 

  15. Denis M, Haidar B, Marcil M, Krimbou L, Genest J (2004) Molecular and cellular physiology of apolipoprotein A-I lipidation by the ATP biding cassette A1 (ABCA1). J Biol Chem 279:7384-7394

    Article  CAS  PubMed  Google Scholar 

  16. Haidar B, Denis M, Marcil M, Krimbou L, Genest J. Apolipoprotein A-I activates cellular camp signaling through the ABCA1 receptor. Evidence for molecular interactions between ABCA1 receptor and G protein. J Biol Chem. 2004;279:9963-9969

    Google Scholar 

  17. Chau P, Nakamura Y, Fielding CJ, Fielding PE (2006) Mechanism of prebeta-HDL formation and activation. Biochemistry. 45(12):3981-3987

    Article  CAS  PubMed  Google Scholar 

  18. Li XA, Titlow WB, Jackson BA et al. (2002) High density lipoprotein binding to scavenger receptor, class B, type I activates endothelial nitric-oxide synthase in a ceramide-dependent manner. J Biol Chem 277:11058

    Article  CAS  PubMed  Google Scholar 

  19. Van Eck M, Singaraja RR, Ye D, Hildebrand RB, James ER, Hayden MR, Van Berkel TJ (2006) Macrophage ATP-binding cassette transporter A1 overexpression inhibits atherosclerotic lesion progression in low-density lipoprotein receptor knockout mice. Arterioscler Thromb Vasc Biol 26(4):929-934

    Article  PubMed  Google Scholar 

  20. Barter PJ, Ballantyne CM, Carmena R et al. (2006) Apo B versus cholesterol in estimating cardiovascular risk and in guiding therapy: report of the thirty-person/ten-country panel. J Intern Med 259(3):247-258

    Article  CAS  PubMed  Google Scholar 

  21. Grundy SM, Cleeman JI, Daniels SR, et al.; American Heart Association; National Heart, Lung, and Blood Institute. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005; 112(17):2735-2752

    Google Scholar 

  22. Sjarif DR, Sinke RJ, Duran M et al. (1998) Clinical heterogeneity and novel mutations in the glycerol kinase gene in three families with isolated glycerol kinase deficiency. J Med Genet 35:650

    Article  CAS  PubMed  Google Scholar 

  23. Santamarina-Fojo S: The familial chylomicronemia syndrome. Endocrinol Metab Clin North Am. 1998;27:551, viii

    Google Scholar 

  24. Weinstock PH, Bisgaier CL, Aalto-Setala K et al. (1995) Severe hypertriglyceridemia, reduced high density lipoprotein, and neonatal death in lipoprotein lipase knockout mice: Mild hypertriglyceridemia with impaired very low density lipoprotein clearance in heterozygotes. J Clin Invest 96: 2555

    Article  CAS  PubMed  Google Scholar 

  25. Mahley RW, Huang Y, Rall SC Jr (1999) Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia): Questions, quandaries, and paradoxes. J Lipid Res 40:1933

    CAS  PubMed  Google Scholar 

  26. Zhang SH, Reddick RL, Piedrahita JA, Maeda N (1992) Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science 258:468

    Article  CAS  PubMed  Google Scholar 

  27. Pajukanta P, Lilja HE, Sinsheimer JS et al. (2004) Familial combined hyperlipidemia is associated with upstream transcription factor 1 (USF1). Nat Genet 36(4):371-376

    Article  CAS  PubMed  Google Scholar 

  28. Kalant D, MacLaren R, Cui W, Samanta R, Monk PN, Laporte SA, Cianflone K (2005) C5L2 is a functional receptor for acylation-stimulating protein. J Biol Chem 280(25): 23936-23944

    Article  CAS  PubMed  Google Scholar 

  29. Wilson DJ, Gahan M, Haddad L et al. (1998) A World Wide Web site for low-density lipoprotein receptor gene mutations in familial hypercholesterolemia: Sequence-based, tabular, and direct submission data handling. Am J Cardiol 81:1509

    Article  CAS  PubMed  Google Scholar 

  30. Whitfield AJ, Barrett PH, van Bockxmeer FM, Burnett JR (2004) Lipid disorders and mutations in the APOB gene. Clin Chem 50(10):1725-1732

    Article  CAS  PubMed  Google Scholar 

  31. Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH (2006) Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 354(12): 1264-1272

    Article  CAS  PubMed  Google Scholar 

  32. Garuti R, Jones C, Li WP, Michaely P, Herz J, Gerard RD, Cohen JC, Hobbs HH. The modular adaptor protein autosomal recessive hypercholesterolemia (ARH) promotes low density lipoprotein receptor clustering into clathrin-coated pits. J Biol Chem. 2005;280(49):40996-41004

    Google Scholar 

  33. Berge KE, Tian H, Graf GA et al. (2000) Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science 290:1771

    Article  CAS  PubMed  Google Scholar 

  34. Mooser V, Mancini FP, Bopp S et al. (1995) Sequence polymorphisms in the apo(a) gene associated with specific levels of Lp(a) in plasma. Hum Mol Genet 4:173

    Article  CAS  PubMed  Google Scholar 

  35. Danesh J, Collins R, Peto R (2000) Lipoprotein(a) and coronary heart disease: Meta-analysis of prospective studies. Circulation 102:1082

    CAS  PubMed  Google Scholar 

  36. Dastani Z, Engert JC, Genest J, Marcil M. Genetics of high-density lipoproteins. Curr Opin Cardiol. 2006;21(4): 329-335

    Google Scholar 

  37. Lewis GF, Rader DJ (2005) New insights into the regulation of HDL metabolism and reverse cholesterol transport. Circ Res 96(12):1221-1232

    Article  CAS  PubMed  Google Scholar 

  38. Sorci-Thomas MG, Thomas MJ (2002) The effects of altered apolipoprotein A-I structure on plasma HDL concentration. Trends Cardiovasc Med 12:121

    Article  CAS  PubMed  Google Scholar 

  39. Boekholdt SM, Kuivenhoven JA, Hovingh GK, Jukema JW, Kastelein JJ, van Tol A (2004) CETP gene variation: relation to lipid parameters and cardiovascular risk. Curr Opin Lipidol 15(4):393-398

    Article  CAS  PubMed  Google Scholar 

  40. Calabresi L, Pisciotta L, Costantin A et al. (2005) The molecular basis of lecithin:cholesterol acyltransferase deficiency syndromes: a comprehensive study of molecular and biochemical findings in 13 unrelated Italian families. Arterioscler Thromb Vasc Biol 25(9):1972-1978

    Article  CAS  PubMed  Google Scholar 

  41. Brooks-Wilson A, Marcil M, Clee SM et al. (1999) Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency. Nat Genet 22(4):336-345

    Article  CAS  PubMed  Google Scholar 

  42. Marcil M, Brooks-Wilson A, Clee SM et al. (1999) Mutations in the ABC1 gene in familial HDL deficiency with defective cholesterol efflux. Lancet 354:1341

    Article  CAS  PubMed  Google Scholar 

  43. Carstea ED, Morris JA, Coleman KG et al. (1997) Niemann-Pick C1 disease gene: Homology to mediators of cholesterol homeostasis. Science 277:228

    Article  CAS  PubMed  Google Scholar 

  44. Choi HY, Karten B, Chan T, Vance JE, Greer WL, Heidenreich RA, Garver WS, Francis GA (2003) Impaired ABCA1-dependent lipid efflux and hypoalphalipoproteinemia in human Niemann-Pick type C disease. J Biol Chem 278(35):32569-32577

    Article  CAS  PubMed  Google Scholar 

  45. Lee CY, Lesimple A, Denis M, Vincent J, Larsen A, Mamer O, Krimbou L, Genest J, Marcil M (2006) Increased sphingomyelin content impairs HDL biogenesis and maturation in human Niemann-Pick disease type B. J Lipid Res 47(3): 622-632

    Article  CAS  PubMed  Google Scholar 

  46. Anderson GL, Limacher M, Assaf AR (2004) Effects of conjugated equine estrogen in post-menopausal women with hysterectomy: The Women’s Health Initiative randomized controlled trial. JAMA 291:1701

    Article  CAS  PubMed  Google Scholar 

  47. Meigs JB, Wilson PW, Fox CS, Vasan RS, Nathan DM, Sullivan L, D’Agostino RB. Body mass index, metabolic syndrome and risk of type 2 diabetes or cardiovascular disease. J Clin Endocrinol Metab. 2006 May 30

    Google Scholar 

  48. Kahn R, Buse J, Ferrannini E, Stern M; American Diabetes Association; European Association for the Study of Diabetes. The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2005;28(9):2289-2304

    Google Scholar 

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Author information

Authors and Affiliations

  1. Division of Cardiology, McGill University Health Center/Royal Victoria Hospital, 687 Pine Avenue West, Montreal, QC, Canada, H3A 1A1

    Jacques Genest

Authors
  1. Khalid Alwaili
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  2. Khalid Alrasadi
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  3. Zari Dastani
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  4. Iulia Iatan
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  5. Zuhier Awan
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  6. Jacques Genest
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Corresponding author

Correspondence to Jacques Genest .

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Editors and Affiliations

  1. Masonic Medical Research Laboratory, Bleecker St. 2150, Utica, 13501, U.S.A.

    Ramon Brugada

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Alwaili, K., Alrasadi, K., Dastani, Z., Iatan, I., Awan, Z., Genest, J. (2010). Genetic Lipoprotein Disorders and Cardiovascular Disease. In: Brugada, R. (eds) Clinical Approach to Sudden Cardiac Death Syndromes. Springer, London. https://doi.org/10.1007/978-1-84882-927-5_17

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  • DOI: https://doi.org/10.1007/978-1-84882-927-5_17

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